Trisubstituted methyl alcohols and their polymerizable derivatives

ABSTRACT

Provided herein are trisubstituted methyl alcohols, preferably pH indicators that are substituted with optionally substituted aryl and or optionally substituted heteroaryl groups, and optionally include one or more polymerizable substituents.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. provisional application Ser.No. 61/570,626, filed Dec. 14, 2011, and Ser. No. 61/698,427, filed Sep.7, 2012. These applications are hereby incorporated by reference intheir entireties.

FIELD OF THE INVENTION

This invention relates to trisubstituted methyl alcohols that aresubstituted with optionally substituted aryl and or optionallysubstituted heteroaryl groups, which preferably act as pH indicators.This invention also relates to such trisubstituted methyl alcohols thatcontain one or more polymerizable functional groups so as to participatewith polymerizable monomers in polymer formation.

BACKGROUND OF THE INVENTION

Triarylmethyl indicator compounds that detect the presence of acidicmolecules are useful, for example to detect the presence of bacteria infoods, wounds, and the like. To detect bacterial growth, the indicatoris included in a polymeric matrix that contacts, for example, the woundor the food. If the indicator is not covalently bound to the polymericmatrix, there is a possibility that the indictor can leach out of thepolymeric matrix and mix with the food or wound. While this problem canbe addressed by cross-linking the polymer to entrap the indicator, thereare many examples where the polymers are not desirably cross-linked.Moreover, cross-linking is not an absolute assurance that a small amountof the indicator will still not leach.

Hexamethoxy red and heptamethoxy red are preferred pH indicators as theyare transparent at pH's of about 6 and above, and bright red/purple atlower pHs. The use of such indicators is beneficial as it provides anaccurate visual analysis of the presence of bacterial growth. Whilethere exists numerous ways to modify pH indicators to include apolymerizable group, it is essential that such modification does notsignificantly alter the pKa of the so modified indicator so that theindicator retains its underlying detection characteristics. Providedhere are triarylmethyl indicators which can detect a wide range ofacidity, and/or that comprise one or more polymerizable groups. Thesepolymerizable groups are introduced in such a manner that the pKa ofthese indicators is not materially altered.

SUMMARY OF THE INVENTION

Provided herein are novel trisubstituted methyl alcohols of Formula A:

wherein each of ring A, ring B, and ring C independently represent anaryl or a heteroaryl optionally substituted with substituents as definedherein, for example, in Formulas (I) and (II), with the proviso that acompound of Formula (A) excludes pentamethoxy red, hexamethoxy red, orheptamethoxy red. Preferred aryl groups include phenyl and naphthyl.Preferred heteroaryl groups include furanyl, benzofuranyl, thiophenyl,benzothiophenyl and such other electron rich, neutral (i.e., neitherbasic nor alkaline) heteroaryls. Preferred compounds of Formula (A) areneutral, as defined above. More preferred compounds of Formula (A) arethose that undergo a protonation and removal of the hydroxy group, and aconcomitant generation of colored cation at a pH of 4.5 to 6:

In certain aspects, all three rings of Formula (A) are aryl. In certainother aspects, two of the rings of Formula (A) are aryl. In certainother aspects, one of the rings of Formula (A) are aryl. In certainother aspects, none of the rings of Formula (A) are aryl.

In one aspect, provided herein are compounds of Formulas (I) and (II):

wherein

-   -   each of p, q, and r independently are, 0, 1, or 2, provided that        the compound of Formula (II) excludes pentamethoxy red,        hexamethoxy red, and heptamethoxy red;    -   each X independently is a substituent that is:        -   C₁-C₆ alkyl, optionally substituted with 1-3 phenyl, oxo,            cyano, halo, nitro;        -   vinyl optionally substituted with 1-3 C₁-C₆ alkyl, phenyl,            or naphthyl, wherein the phenyl or naphthyl is substituted            with 1-3 C₁-C₆ alkoxy, cyano, halo, or nitro;        -   ethynyl optionally substituted with 1-3 C₁-C₆ alkyl, phenyl,            or naphthyl, wherein the phenyl or naphthyl is substituted            with 1-3 C₁-C₆ alkoxy, cyano, halo, or nitro;        -   —COR³⁰, wherein R³⁰ is hydrogen, C₁-C₆ alkyl, phenyl,            napthyl, or an oxime thereof;        -   phenyl or naphthyl, preferably phenyl, optionally            substituted with 1-4, preferably 1-3, more preferably 1-2,            and still more preferably 1 substituent, wherein the            substituent is selected from the group consisting of alkyl,            preferably C₁-C₆ alkyl, —OR¹⁸, wherein R¹⁸ is alkyl,            preferably C₁-C₆ alkyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl,            preferably phenyl, each of which are optionally substituted            with 1-5, preferably, 1-3 substituents selected from the            group consisting of halo, preferably fluoro, cyano, C₁-C₆            alkoxy, and aryloxy;        -   —OR¹⁹, wherein R¹⁹ is hydrogen, C₁-C₆ alkyl, C₃-C₈            cycloalkyl, or phenyl, each of which are optionally            substituted with 1-5, preferably, 1-3 substituents selected            from the group consisting of halo, preferably fluoro, cyano,            nitro, C₁-C₆ alkoxy, and aryloxy, or R¹⁹ is Pg; or cyano,            halo, nitro;    -   Pg is a hydroxyl protecting group;    -   each R¹⁷ independently is hydrogen or X, wherein X is defined as        above;    -   R¹ is hydrogen, X, or —OR⁸, wherein X is defined as above;    -   each of R²-R⁸ independently is hydrogen, Pg, C₁-C₄ alkyl or is        -L-R⁹;    -   R⁹ is a polymerizable group;    -   L is a covalent bond or a linker which joins the one or more        polymerizable groups to the oxygen atom to which it is attached;    -   provided that for Formula (II), if p+q+r=0, then at least one,        preferably 2, more preferably 3, still more preferably 4, and        yet more preferably 5 of R¹⁷ groups are X.

In one embodiment, the compound provided is of Formula (I-A):

wherein

-   -   R¹ is hydrogen, —OH, —OPg or —OR⁸;    -   each of R²-R⁸ independently is hydrogen, Pg, C₁-C₄ alkyl or is        -L-R⁹ provided that at least one of R²-R⁸ is -L-R⁹; and    -   R⁹, Pg, and L are defined as above.

Within the aspects and embodiments provided herein, in one embodiment,R¹ is —OR⁸, and each of R²-R⁸ independently is Pg, C₁-C₄ alkyl or -L-R⁹,provided that at least one of R²-R⁸ is -L-R⁹. In another embodiment, atleast one of R²-R⁸ is hydrogen or R¹ is —OH. In a preferred embodiment,p+q+r is 3, more preferably, p+q+r is 2, and yet more preferably, p+q+ris 1.

In yet another preferred embodiment, provided herein is a compound ofFormula (II), of Formula (I-B):

where X¹-X³ are independently hydrogen or are defined as X in Formula(I), and R¹-R⁷ are defined as in Formula (I).

In yet another preferred embodiment, provided herein is a compound ofFormula (II), of Formula (II-A):

where X¹-X³ are independently hydrogen or are defined as X in Formula(I), and R²¹-R²³ are independently hydrogen or defined as X in Formula(I).

As used herein, a polymerizable group preferably refers to a group thatincludes a vinyl moiety that is polymerized under various well knowncondition with monomers containing a vinyl moiety. A polymerizable groupalso includes a moiety that can react with an electrophile or anucleophile, preferably readily, to form a covalent linkage.Non-limiting examples include, —N═C═O, N═C═S, CO₂Ar_(F), azide, ethynyl,and the like. As used herein Ar_(F) refers to a pentafluoro ortetrafluoro phenyl group. Leaving groups other than —OAr_(F) are wellknown to the skilled artisan and useful herein, and will be apparent tothe skilled artisan upon reading this disclosure. Other polymerizablegroups are well known to the skilled artisan and will be apparent tothem upon reading this disclosure.

Also provided herein are polymers which contain trisubstituted methylalcohol indicator covalently bound to the polymer wherein sufficientindicator is bound to the polymer such that the color of the polymer ischanged from transparent at neutral pH to colored at acidic pH.

DETAILED DESCRIPTION OF THE INVENTION

This invention relates to trisubstituted methyl alcohols andpolymerizable forms thereof. Before describing this invention in detailthe following terms are defined.

DEFINITIONS

“Alkyl” refers to monovalent saturated aliphatic hydrocarbyl groupshaving from 1 to 10 carbon atoms and, in some embodiments, from 1 to 6carbon atoms. This term includes, by way of example, linear and branchedhydrocarbyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl,isobutyl, sec-butyl, t-butyl, n-pentyl, and neopentyl.

“C_(x)—C_(y)” with respect to a group refers to that group having from xto y carbon atoms.

“Alkylene” refers to divalent saturated aliphatic hydrocarbyl groupshaving from 1 to 25 carbon atoms and, in some embodiments, from 1 to 15carbon atoms. The alkylene groups include branched and straight chainhydrocarbyl groups, such as methylene, ethylene, propylene,2-methypropylene, pentylene, and the like.

“Heteroalkylene” refers to alkylene wherein 1-8 carbon atoms, arereplaced with a heteroatom, preferably, with one or more of —N(COR′)—,—S—, —S(O)—, —S(O₂)—, and —O—, where R′ is C₁-C₆ alkyl.

“Alkoxy” refers to the group —O-alkyl, and includes, by way of example,methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, t-butoxy, sec-butoxy,and n-pentoxy.

“Aryl” refers to an aromatic group of from 6 to 14 carbon atoms and noring heteroatoms and having a single ring (e.g., phenyl) or multiplecondensed (fused) rings (e.g., naphthyl or anthryl). For multiple ringsystems, the term “Aryl” applies when the point of attachment is at anaromatic carbon atom (e.g., 5,6,7,8 tetrahydronaphthalene-2-yl is anaryl group as its point of attachment is at the 2-position of thearomatic phenyl ring).

“Heteroaryl” refers to an aromatic group of from 5 to 14 ring atoms and1-3 ring heteroatoms and having a single ring (e.g., furyl) or multiplecondensed (fused) rings (e.g., benzofuryl). For multiple ring systems,the term “heteroaryl” applies when the point of attachment is at anaromatic ring atom containing at least one heteroatom.

“Aryloxy” refers to the group —O-Aryl.

“Halo” refers to F, Cl, Br, and/or I.

“Heteroatom” refers to nitrogen, sulfur, phosphorous, an oxidized formsthereof, and/or oxygen.

“Pg” refers to a protecting group. Protecting group are well knownfunctional groups that when bound to a functional group, render theresulting protected functional group inert to the reaction to beconducted on other portions of the compound and the correspondingreaction condition, and which can be reacted to regenerate the originalfunctionality under deprotection conditions. The protecting group isselected to be compatible with the remainder of the molecule. An —O-Pggroup protects a hydroxyl functionality during the synthesis describedhere. Examples of hydroxyl protecting groups include, for instance,ethers such as benzyl, p-methoxybenzyl, p-nitrobenzyl, allyl, andtrityl; dialkylsilylethers, such as dimethylsilyl ether, andtrialkylsilyl ethers such as trimethylsilyl ether, triethylsilyl ether,and t-butyldimethylsilyl ether; esters such as benzoyl, acetyl,phenylacetyl, formyl, mono-, di-, and trihaloacetyl such aschloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl; andcarbonates such as methyl, ethyl, 2,2,2-trichloroethyl, allyl, andbenzyl. Additional examples of hydroxy protecting groups are found instandard reference works such as Greene and Wuts, Protective Groups inOrganic Synthesis., 2d Ed., 1991, John Wiley & Sons, and McOmieProtective Groups in Organic Chemistry, 1975, Plenum Press. Methods forprotecting and deprotecting hydroxyl groups disclosed herein can befound in the art, and specifically in Greene and Wuts, supra, and thereferences cited therein.

“Leaving group” refers to a moiety that can be replaced by anucleophile. Examples of leaving groups include but are not limited tohalo and sulfonates.

As used herein, “polymers” provided herein do not include polymerscreated by substitution of a substitution. Should such substitution ofsubstitution give rise to potential polymers, such substitution islimited to 3 such substitutions.

Referring to the compound of Formula (I), in one embodiment, each ofR²-R⁸ independently is C₁-C₄ alkyl or is -L-R⁹. In another embodiment,1-7 of R²-R⁸ are -L-R⁹. In another embodiment, 2-7 or 3-6 of R²-R⁸ are-L-R⁹. In another embodiment, 1-6 of R²-R⁸ is C₁-C₄ alkyl. In anotherembodiment, 1-6 of R²-R⁸ is methyl. In another embodiment, at least oneof R²-R⁸ is hydrogen.

In another embodiment, the polymerizable group is selected from thegroup consisting of —NCO, —NCS, —CO₂R¹¹, -ethynyl, —N₃, allyl or is

wherein

R¹⁰ is selected from the group consisting of hydrogen, C₁-C₆ alkyl,CO₂H, CO₂R¹², CN, and CON(R¹³)₂;

R¹¹ is a phenyl substituted with 4 or 5 fluoro atoms, or is succinimidylor phthalimidyl;

R¹² is C₁-C₁₂ alkyl optionally substituted with 1-3 hydroxy groups;

R¹³C₁-C₁₂ alkyl optionally substituted with 1-3 hydroxy groups or the 2R¹³ groups together with the nitrogen atoms they are bound to form a 5-7membered heterocyclic ring having 1 to 3 heteroatoms selected fromoxygen, sulfur, nitrogen or NR¹⁴ where R¹⁴ is hydrogen or C₁-C₁₂ alkyl;

R¹⁵ is selected from the group consisting of hydrogen, C₁-C₆ alkyloptionally substituted with 1-3 hydroxy groups, and CN;

Y is O or NR¹⁶; and

R¹⁶ is hydrogen or C₁-C₆ alkyl.

In another embodiment, L is C₁-C₂₀ alkylene or heteroalkylene having 1to 5 heteroatoms selected from oxygen, sulfur, and nitrogen, each ofwhich is optionally substituted with 1-10 substituents selected from thegroup consisting of oxo (═O), thio (═S), and C₁-C₆ alkyl. Non-limitingexamples of alkylene include —(CH₂)_(n)— where n is 1-12. In anotherembodiment, L is a covalent bond.

In another embodiment, the compound of Formula (I) is of Formula (I-B):

wherein

-   -   R¹ is hydrogen or —OR²⁰;    -   each R²⁰ independently is methyl, vinyl, allyl,        —(CH₂)_(m)—OCOCH═CH₂, or —(CH₂)_(m)—OCOC(Me)═CH₂, provided that        at least one R²⁰ is not methyl; and    -   m is 2-10.

In another embodiment, for the compound of Formula (I-B), 1, 2, or 3 R²⁰groups are vinyl or allyl. In another embodiment, for the compound ofFormula (I-B), 1, 2, or 3 R²⁰ groups are —(CH₂)_(m)OCOC(Me)═CH₂. Inanother embodiment, for the compound of Formula (I-B), 1, 2, or 3 R²⁰groups are —(CH₂)_(m)—OCOCH═CH₂. Such groups will result in theformation of an ethylene, propylene, or another higher alkylene groupcovalently attached at one end to the remainder of the indicator and atthe other end to the polymeric chain. A polymerizable group, such as anacrylate or a methacrylate, is contemplated to polymerize the compoundsof this invention with another monomer such as hydroxyethylmethacrylate. As these groups mimic the methyl group of the methoxymoiety of both hexamethoxy red and heptamethoxy red, their inclusionshould minimally alters the pKa of the indicator. That is to say thatthe pKa should changed by no more than ±0.5, preferably by no more than±0.3, and even preferably by no more than ±0.2 units.

The inclusion of one or more X substituents on the phenyl ring(s) allowfor modulating the pKa of the indicator or for modulating the stabilityof the trisubstituted methyl cation formed when the hydroxy group isprotonated and leaves as water, in a manner consistent with the pHdesired for color transformation of the indicator. A nonlimiting processof water elimination and color generation is schematically depictedbelow:

wherein each Ar independently refers to aryl moieities shown in thecompounds provided herein, for example, of Formula (I) and (II). That isto say that introducing an electron donating and/or a cation stabilizingsubstituent such as, without limitation, alkoxy, alkyl, and aryl,provide an indicator, which changes color at lower acidity and higherpH. On the other hand, introducing an electron withdrawing substituentsuch, without limitation, halo or cyano, will provide for an indicator,which changes color at higher acidity and lower pH.

The compounds of this invention are synthesized following art recognizedmethods with the appropriate substitution of commercially availablereagents as needed. Other compounds are synthesized followingmodifications of the methods illustrated herein, and those known, basedon this disclosure. See, for example, Raj. B. Durairaj, Resorcinol:Chemistry, Technology, and Applications, Birkhäuser, 2005. Illustrativeand non-limiting methods for synthesizing the compounds of thisinvention are schematically shown below which show the synthesis of anintermediate 4-hydroxyphenyl compound. Such intermediates are alsowithin the scope of this invention. That compound is subsequentlymodified on the hydroxyl group to incorporate the polymerizable group.

In step 1, a protected resorcinol methyl ether is brominated, preferablyusing 1 equivalent of bromine in a non-polar solvent such as dioxane. Asused herein, PG refers to a protecting group, which refers to well knownfunctional groups that, when bound to a functional group, render theresulting protected functional group inert to the reaction to beconducted on other portions of the compound and the correspondingreaction condition, and which can be reacted to regenerate the originalfunctionality under deprotection conditions. Examples of protectinggroups useful for synthesizing the compounds of this invention, andmethods for protection and deprotection employed herein, are found instandard reference works such as Greene and Wuts, Protective Groups inOrganic Synthesis., 2d Ed., 1991, John Wiley & Sons, and McOmieProtective Groups in Organic Chemistry, 1975, Plenum Press.Methylthiomethyl ether and allyl ethers are certain non-limitingprotecting groups contemplated for the scheme above. In step 2, thebrominated resorcinol derivative is metalated to provide a Grignardreagent or a resorcyl lithium. In step 3, the metalated aryl is reactedwith an aryl carboxylic acid ester to provide a protected precursor tothe compound of Formula (I), which is deprotected in step 4.

In step 5, the deprotected phenolic hydroxy compound is reacted with anR⁹-L moiety containing a leaving group such as chloro, bromo, iodo, or—OSO₂R_(S) where R_(S) is C₁-C₆ alkyl optionally substituted with 1-5fluoro atoms or aryl optionally substituted with 1-3 C₁-C₆ alkyl or halogroups. Alternatively, the deprotected compound is reacted with acompound that provides part of the linker L (step 6). Such compounds areelaborated to a compound of this invention as shown in steps 7 and 8below using reagents and methods well known to the skilled artisan.

The compounds of Formula (I) are also synthesized by reacting anappropriately protected aryl carboxylic acid ester with the metalatedaryl compound and elaborating the triaryl methyl compounds produced, viamethods provided herein and/or via methods well known to the skilledartisan:

The compounds of Formula (I) are also synthesized by reacting anappropriately protected aryl carboxylic acid ester with the metalatedaryl compound and elaborating the triaryl methyl compounds produced, viamethods provided herein and/or via methods well known to the skilledartisan:

Compounds of Formula (I-B) are synthesized, for example, starting fromcommercially available hexamethoxy red or heptamethoxy red as shownbelow.

The demethylation can be performed following various methods well knownin the art, such as, for example, reacting with an alkyl thiolate, suchas isopropyl thiolate, ethyl thiolate, or diethylaminoethyl thiolate, orreacting with amides such as NaN(SiMe₃) and LiN(i-Pr)₂. See also Greeneand Wuts supra. Various alkali metal carbonates are useful bases.

Other compounds of this invention are conveniently synthesized followingthese and other known methods upon appropriate substitution of startingmaterial and, if needed, protecting groups. Electron withdrawingsubstituents such as halo can be conveniently incorporated into the arylrings by electrophilic substitution employing hypohalite, halogens, ICl,preferably under alkaline conditions. A halo group is convenientlyconverted to a cyano group following well known methods, such as thoseemploying CuCN. A nitro group is conveniently incorporated byelectrophilic nitration employing various conditions and reagents wellknown to the skilled artisan, such as nitronium tetrafluoroborate,nitric acid, optionally with acetic anhydride, and the likes.

Other compounds of this invention, for example, those including one ormore heteroaryl A, B, and C rings, are prepared following methods wellknown to the skilled artisan, or following methods illustrated here,upon appropriate substitution of starting material and reactionconditions as will be apparent to the skilled artisan upon reading thisdisclosure.

The reactions are carried out, preferably in an inert solvent, for aperiod of time sufficient to provide a substantial amount of theproduct, which is detected following well known methods such as thinlayer chromatography or ¹H-nuclear magnetic resonance spectrometry. Theproducts are used for the subsequent steps without further purificationor can be purified following well known methods such as one or more ofcolumn chromatography, crystallization, precipitation, and distillationunder reduced pressure.

Other compounds of this invention are prepared following methods wellknown to a skilled artisan and/or those disclosed herein uponappropriate substitution of reactants and reagents.

It is contemplated that the pH sensitivity of the compounds of Formulas(I) and (II), wherein R¹ is hydrogen, is within ±0.5, preferably, within±0.3, more preferably within ±0.2 of that of hexamethoxy red. It is alsocontemplated that pH sensitivity of the compounds of Formula (I),wherein R¹ is —OR⁸, is within ±0.5, preferably, within ±0.3, morepreferably within ±0.2 of that of heptamethoxy red. Compounds within thescope of this invention include but are not limited to those set forthin the Tables below.

Preferred Compounds of Formula (I-A)

TABLE 1 Ex. R₂, R₄, No. R₁ R₆ R₃ R₅ R₇ 1 H —CH₃ —CH₃ —CH₃ —CH₂CH═CH₂ 2 H—CH₃ —CH₂CH═CH₂ —CH₃ —CH₃ 3 H —CH₃ —CH₃ —CH₂CH═CH₂ —CH₃ 4 H —CH₃—CH₂CH═CH₂ —CH₂CH═CH₂ —CH₃ 5 H —CH₃ —CH₃ —CH₂CH═CH₂ —CH₂CH═CH₂ 6 H —CH₃—CH₂CH═CH₂ —CH₃ —CH₂CH═CH₂ 7 H —CH₃ —CH₂CH═CH₂ —CH₂CH═CH₂ —CH₂CH═CH₂ 8 H—CH₃ —CH₃ —CH₃ —CH₂CH₂OC(O)CH═CH₂ 2-(acryl)ethylene 9 H —CH₃ —CH₃2-(acryl)ethylene —CH₃ 10 H —CH₃ 2-(acryl)ethylene 2-(acryl)ethylene—CH₃ 11 H —CH₃ Allyl acrylate —CH₃ 12 H —CH₃ —(CH₂)_(n)NCO where—(CH₂)_(n)NCS where —CH₃ n = 2-12 n = 2-12 13 H —CH₃ —(CH₂)nNCO where—(CH₂)_(n)NCO where —CH₃ n = 2-12 n = 2-12 14 H —CH₃ —(CH₂)_(n)NCS where—(CH₂)_(n)NCS where —CH₃ n = 2-12 n = 2-12 15 H —CH₃ —(CH₂)_(n)CO₂Ar_(F)—(CH₂)_(n)CO₂Ar_(F) —CH₃ where Ar_(F) is penta or where Ar_(F) is pentaor tetrafluorophenyl tetrafluorophenyl 16 H —CH₃ —(CH₂)_(n)N₃ where—(CH₂)_(n)N₃ where —CH₃ n = 2-12 n = 2-12 17 H —CH₃ —(CH₂)_(n)CCH where—(CH₂)_(n)CCH where —CH₃ n = 2-12 n = 2-12 18 H —CH₃ —(CH₂)_(n)NCO where—(CH₂)_(n)NCO where —CH₃ n = 2-12 n = 2-12 19 H —CH₃ —CH₃ —(CH₂)_(n)NCSwhere —CH₃ n = 2-12 20 H —CH₃ —CH₃ —(CH₂)_(n)CO₂Ar_(F) —CH₃ where ArF ispenta or tetrafluorophenyl 21 H —CH₃ —CH₃ —(CH₂)_(n)N₃ where —CH₃ n =2-12 22 H —CH₃ —CH₃ —(CH₂)_(n)CCH where —CH₃ n = 2-12 23 —OMe —CH₃ —CH₃—CH₃ —CH₂CH═CH₂ 24 —OMe —CH₃ —CH₂CH═CH₂ —CH₃ —CH₃ 25 —OMe —CH₃ —CH₃—CH₂CH═CH₂ —CH₃ 26 —OMe —CH₃ —CH₂CH═CH₂ —CH₂CH═CH₂ —CH₃ 27 —OMe —CH₃—CH₃ —CH₂CH═CH₂ —CH₂CH═CH₂ 28 —OMe —CH₃ —CH₂CH═CH₂ —CH₃ —CH₂CH═CH₂ 29—OMe —CH₃ —CH₂CH═CH₂ —CH₂CH═CH₂ —CH₂CH═CH₂ 30 —OMe —CH₃ —CH₃ —CH₃—CH₂CH₂OC(O)CH═CH₂ 2-(acryl)ethylene 31 —OMe —CH₃ —CH₃ 2-(acryl)ethylene—CH₃ 32 —OMe —CH₃ 2-(acryl)ethylene 2-(acryl)ethylene —CH₃ 33 —OMe —CH₃Allyl acrylate —CH₃ 34 —OMe —CH₃ —(CH₂)_(n)NCO where —(CH₂)_(n)NCS where—CH₃ n = 2-12 n = 2-12 35 —OMe —CH₃ —(CH₂)_(n)NCO where —(CH₂)_(n)NCOwhere —CH₃ n = 2-12 n = 2-12 36 —OMe —CH₃ —(CH₂)_(n)NCS where—(CH₂)_(n)NCS where —CH₃ n = 2-12 n = 2-12 37 —OMe —CH₃—(CH₂)_(n)CO₂Ar_(F) —(CH₂)_(n)CO₂Ar_(F) —CH₃ where Ar_(F) is penta orwhere Ar_(F) is penta or tetrafluorophenyl tetrafluorophenyl 38 —OMe—CH₃ —(CH₂)_(n)N₃ where —(CH₂)_(n)N₃ where —CH₃ n = 2-12 n = 2-12 39—OMe —CH₃ —(CH₂)_(n)CCH where —(CH₂)_(n)CCH where —CH₃ n = 2-12 n = 2-1240 —OMe —CH₃ —(CH₂)_(n)NCO where —(CH₂)_(n)NCO where —CH₃ n = 2-12 n =2-12 41 —OMe —CH₃ —CH₃ —(CH₂)_(n)NCS where —CH₃ n = 2-12 42 —OMe —CH₃—CH₃ —(CH₂)_(n)CO₂Ar_(F) —CH₃ where Ar_(F) is penta or tetrafluorophenyl43 —OMe —CH₃ —CH₃ —(CH₂)_(n)N₃ where —CH₃ n = 2-12 44 —OMe —CH₃ —CH₃—(CH₂)_(n)CCH where —CH₃ n = 2-12 45 H —CH₃ —(CH₂)_(n)OC(O)-—(CH₂)_(n)OC(O)- —CH₃ CH═CH₂ where CH═CH₂ where n = 2-12 n = 2-12 46 H—CH₃ —CH₃ —(CH₂)_(n)OC(O)- —CH₃ CH═CH₂ where n = 2-12 47 —OMe —CH₃—(CH₂)_(n)OC(O)- —(CH₂)_(n)OC(O)- —CH₃ CH═CH₂ where CH═CH₂ where n =2-12 n = 2-12 48 —OMe —CH₃ —CH₃ —(CH₂)_(n)OC(O)- —CH₃ CH═CH₂ where n =2-12

Preferred compounds of Formula (I-B):

TABLE 2 Ex. R², No. R¹ R⁴, R⁶ R³ R⁵ R⁷ X¹ X² X³ 1 H —CH₃ —CH₃ —CH₃—CH₂CH═CH₂ H/—OMe/ H/—OMe/ OMe/ Me/Ar¹ Me/Ar¹ Me/ Ar¹ (refers Ar¹ tophenyl and 4- methoxy phenyl) 2 H —CH₃ —CH₂CH═CH₂ —CH₃ —CH₃ H/—OMe/H/—OMe/ OMe/ Me/Ar¹ Me/Ar¹ Me/ Ar¹ 3 H —CH₃ —CH₃ —CH₂CH═CH₂ —CH₃ H/—OMe/H/—OMe/ OMe/ Me/Ar¹ Me/Ar¹ Me 4 H —CH₃ —CH₂CH═CH₂ —CH₂CH═CH₂ —CH₃H/—OMe/ H/—OMe/ /Ar¹ Me/Ar¹ Me/Ar¹ 5 H —CH₃ —CH₃ —CH₂CH═CH₂ —CH₂CH═CH₂H/—OMe/ H/—OMe/ OMe/ Me/Ar¹ Me/Ar¹ Me 6 H —CH₃ —CH₂CH═CH₂ —CH₃—CH₂CH═CH₂ H/—OMe/ H/—OMe/ /Ar¹ Me/Ar¹ Me/Ar¹ 7 H —CH₃ —CH₂CH═CH₂—CH₂CH═CH₂ —CH₂CH═CH₂ H/—OMe/ H/—OMe/ OMe/ Me/Ar¹ Me/Ar¹ Me 8 H —CH₃—CH₃ —CH₃ —CH₂CH₂O—C(O)CH═CH₂ H/—OMe/ H/—OMe/ /Ar¹ (2-(acryl)ethylene)Me/Ar¹ Me/Ar¹ 9 H —CH₃ —CH₃ 2-(acryl)ethylene —CH₃ H/—OMe/ H/—OMe/ OMe/Me/Ar¹ Me/Ar¹ Me 10 H —CH₃ 2-(acryl)ethylene 2-(acryl)ethylene —CH₃H/—OMe/ H/—OMe/ /Ar¹ Me/Ar¹ Me/Ar¹ 11 H —CH₃ Allyl acrylate —CH₃ H/—OMe/H/—OMe/ OMe/ Me/Ar¹ Me/Ar¹ Me 12 H —CH₃ —(CH₂)_(n)NCO —(CH₂)_(n)NCS —CH₃H/—OMe/ H/—OMe/ /Ar¹ where n = 2-12 where n = 2-12 Me/Ar¹ Me/Ar¹ 13 H—CH₃ —(CH₂)_(n)NCO —(CH₂)_(n)NCO —CH₃ H/—OMe/ H/—OMe/ OMe/ where n =2-12 where n = 2-12 Me/Ar¹ Me/Ar¹ Me 14 H —CH₃ —(CH₂)_(n)NCS—(CH₂)_(n)NCS —CH₃ H/—OMe/ H/—OMe/ /Ar¹ where n = 2-12 where n = 2-12Me/Ar¹ Me/Ar¹ 15 H —CH₃ —(CH₂)_(n)CO₂Ar_(F) —(CH₂)_(n)CO₂Ar_(F) —CH₃H/—OMe/ H/—OMe/ OMe/ where Ar_(F) is where Ar_(F) is Me/Ar¹ Me/Ar¹ Mepenta or penta or tetrafluorophenyl tetrafluorophenyl 16 H —CH₃—(CH₂)_(n)N₃ where —(CH₂)_(n)N₃ where —CH₃ H/—OMe/ H/—OMe/ /Ar¹ n = 2-12n = 2-12 Me/Ar¹ Me/Ar¹ 17 H —CH₃ —(CH₂)_(n)CCH —(CH₂)_(n)CCH —CH₃H/—OMe/ H/—OMe/ OMe/ where n = 2-12 where n = 2-12 Me/Ar¹ Me/Ar¹ Me 18 H—CH₃ —(CH₂)_(n)NCO —(CH₂)_(n)NCO —CH₃ H/—OMe/ H/—OMe/ /Ar¹ where n =2-12 where n = 2-12 Me/Ar¹ Me/Ar¹ 19 H —CH₃ —CH₃ —(CH₂)_(n)NCS —CH₃H/—OMe/ H/—OMe/ OMe/ where n = 2-12 Me/Ar¹ Me/Ar¹ Me 20 H —CH₃ —CH₃—(CH₂)_(n)CO₂Ar_(F) —CH₃ H/—OMe/ H/—OMe/ /Ar¹ where Ar_(F) is Me/Ar¹Me/Ar¹ penta or tetrafluorophenyl 21 H —CH₃ —CH₃ —(CH₂)_(n)N₃ where —CH₃H/—OMe/ H/—OMe/ OMe/ n = 2-12 Me/Ar¹ Me/Ar¹ Me 22 H —CH₃ —CH₃—(CH₂)_(n)CCH —CH₃ H/—OMe/ H/—OMe/ /Ar¹ where n = 2-12 Me/Ar¹ Me/Ar¹ 23—OMe —CH₃ —CH₃ —CH₃ —CH₂CH═CH₂ H/—OMe/ H/—OMe/ OMe/ Me/Ar¹ Me/Ar¹ Me 24—OMe —CH₃ —CH₂CH═CH₂ —CH₃ —CH₃ H/—OMe/ H/—OMe/ /Ar¹ Me/Ar¹ Me/Ar¹ 25—OMe —CH₃ —CH₃ —CH₂CH═CH₂ —CH₃ H/—OMe/ H/—OMe/ OMe/ Me/Ar¹ Me/Ar¹ Me 26—OMe —CH₃ —CH₂CH═CH₂ —CH₂CH═CH₂ —CH₃ H/—OMe/ H/—OMe/ /Ar¹ Me/Ar¹ Me/Ar¹27 —OMe —CH₃ —CH₃ —CH₂CH═CH₂ —CH₂CH═CH₂ H/—OMe/ H/—OMe/ OMe/ Me/Ar¹Me/Ar¹ Me 28 —OMe —CH₃ —CH₂CH═CH₂ —CH₃ —CH₂CH═CH₂ H/—OMe/ H/—OMe/ /Ar¹Me/Ar¹ Me/Ar¹ 29 —OMe —CH₃ —CH₂CH═CH₂ —CH₂CH═CH₂ —CH₂CH═CH₂ H/—OMe/H/—OMe/ OMe/ Me/Ar¹ Me/Ar¹ Me 30 —OMe —CH₃ —CH₃ —CH₃ —CH₂CH₂OC(O)CH═CH₂H/—OMe/ H/—OMe/ /Ar¹ 2-(acryl)ethylene) Me/Ar¹ Me/Ar¹ 31 —OMe —CH₃ —CH₃2-(acryl)ethylene —CH₃ H/—OMe/ H/—OMe/ OMe/ Me/Ar¹ Me/Ar¹ Me 32 —OMe—CH₃ 2-(acryl)ethylene 2-(acryl)ethylene —CH₃ H/—OMe/ H/—OMe/ /Ar¹Me/Ar¹ Me/Ar¹ 33 —OMe —CH₃ Allyl acrylate —CH₃ H/—OMe/ H/—OMe/ OMe/Me/Ar¹ Me/Ar¹ Me 34 —OMe —CH₃ —(CH₂)_(n)NCO —(CH₂)_(n)NCS —CH₃ H/—OMe/H/—OMe/ /Ar¹ where n = 2-12 where n = 2-12 Me/Ar¹ Me/Ar¹ 35 —OMe —CH₃—(CH₂)_(n)NCO —(CH₂)_(n)NCO —CH₃ H/—OMe/ H/—OMe/ OMe/ where n = 2-12where n = 2-12 Me/Ar¹ Me/Ar¹ Me 36 —OMe —CH₃ —(CH₂)_(n)NCS —(CH₂)_(n)NCS—CH₃ H/—OMe/ H/—OMe/ /Ar¹ where n = 2-12 where n = 2-12 Me/Ar¹ Me/Ar¹ 37—OMe —CH₃ —(CH₂)_(n)CO₂Ar_(F) —(CH₂)_(n)CO₂Ar_(F) —CH₃ H/—OMe/ H/—OMe/OMe/ where Ar_(F) is where Ar_(F) is Me/Ar¹ Me/Ar¹ Me penta or penta ortetrafluorophenyl tetrafluorophenyl 38 —OMe —CH₃ —(CH₂)_(n)N₃ where—(CH₂)_(n)N₃ where —CH₃ H/—OMe/ H/—OMe/ /Ar¹ n = 2-12 n = 2-12 Me/Ar¹Me/Ar¹ 39 —OMe —CH₃ —(CH₂)_(n)CCH —(CH₂)_(n)CCH —CH₃ H/—OMe/ H/—OMe/OMe/ where n = 2-12 where n = 2-12 Me/Ar¹ Me/Ar¹ Me 40 —OMe —CH₃—(CH₂)_(n)NCO —(CH₂)_(n)NCO —CH₃ H/—OMe/ H/—OMe/ /Ar¹ where n = 2-12where n = 2-12 Me/Ar¹ Me/Ar¹ 41 —OMe —CH₃ —CH₃ —(CH₂)_(n)NCS —CH₃H/—OMe/ H/—OMe/ OMe/ where n = 2-12 Me/Ar¹ Me/Ar¹ Me 42 —OMe —CH₃ —CH₃—(CH₂)_(n)CO₂Ar_(F) —CH₃ H/—OMe/ H/—OMe/ /Ar¹ where Ar_(F) is Me/Ar¹Me/Ar¹ penta or tetrafluorophenyl 43 —OMe —CH₃ —CH₃ —(CH₂)_(n)N₃ where—CH₃ H/—OMe/ H/—OMe/ OMe/ n = 2-12 Me/Ar¹ Me/Ar¹ Me 44 —OMe —CH₃ —CH₃—(CH₂)_(n)CCH —CH₃ H/—OMe/ H/—OMe/ /Ar¹ where n = 2-12 Me/Ar¹ Me/Ar¹ 45H —CH₃ —(CH₂)_(n)OC(O)CH═CH₂ —(CH₂)_(n)OC(O)CH═CH₂ —CH₃ H/—OMe/ H/—OMe/OMe/ where n = 2-12 where n = 2-12 Me/Ar¹ Me/Ar¹ Me 46 H —CH₃ —CH₃—(CH₂)_(n)OC(O)CH═CH₂ —CH₃ H/—OMe/ H/—OMe/ /Ar¹ where n = 2-12 Me/Ar¹Me/Ar¹ 47 —OMe —CH₃ —(CH₂)_(n)OC(O)—CH═CH₂ —(CH₂)_(n)OC(O)—CH═CH₂ —CH₃H/—OMe/ H/—OMe/ OMe/ where n = 2-12 where n = 2-12 Me/Ar¹ Me/Ar¹ Me 48—OMe —CH₃ —CH₃ —(CH₂)_(n)OC(O)—CH═CH₂ —CH₃ H/—OMe/ H/—OMe/ /Ar¹ where n= 2-12 Me/Ar¹ Me/Ar¹

Preferred compounds of Formula (II-A)

TABLE 3 Ex. No. X¹ X² X³ R²¹ R²² R²³ H H OMe OMe OMe OMe H OMe OMe OMeOMe OMe H OMe OMe OMe OMe H H OMe OMe OMe H OMe OMe OMe OMe OMe OMe OMeH H Me OMe OMe OMe H Me Me OMe OMe OMe H Me Me OMe OMe H H Me Me OMe HOMe Me Me OMe OMe OMe OMe Me Me Me OMe OMe OMe H H Me OMe OMe OMe H Ar¹(refers Ar¹ OMe OMe OMe to phenyl and 4- methoxy phenyl) H Ar¹ Ar¹ OMeOMe H H Ar¹ Ar¹ OMe H OMe Ar¹ Ar¹ OMe OMe OMe OMe Ar¹ Ar¹ Ar¹ OMe OMeOMe

Certain preferred compounds of Formula (A)

TABLE 4 Ex. No. A B C furyl optionally furyl optionally furyl optionallysubstituted with 1 or substituted with 1 or substituted with 1 or 2methoxy groups 2 methoxy groups 2 methoxy groups furyl optionally furyloptionally 2,6-dimethoxyphen- substituted with 1 or substituted with 1or yl 2 methoxy groups 2 methoxy groups furyl optionally2,6-dimethoxyphen- 2,6-dimethoxyphen- substituted with 1 or yl yl 2methoxy groups thiophenyl option- thiophenyl option- thiophenyl option-ally substituted with ally substituted with ally substituted with 1 or 2methoxy 1or 2 methoxy 1 or 2 methoxy groups groups groups thiophenyloption- thiophenyl option- 2,6-dimethoxyphen- ally substituted with allysubstituted with yl 1or 2 methoxy 1 or 2 methoxy groups groupsthiophenyl option- 2,6-dimethoxyphen- 2,6-dimethoxyphen- allysubstituted with yl yl 1 or 2 methoxy groups

EXAMPLES Example 1 Preparation of Heptamethoxy Red in Gram Scale Step 1:Synthesis of Methyl 2,4,6-Trimethoxybenzoate

2,4,6-trimethoxybenzoic acid (5.61 g, 26.42 mmol) was suspended in 20 mLof methanol. Concentrated sulfuric acid (1 mL) was added to the mixture,and the reaction heated to reflux for 24 hrs. The reaction was cooled toroom temperature, and the methanol removed in vacuo. The residues weretaken up in 50 mL 5% NaHCO₃ and extracted with hexane until all thesolids had dissolved. The hexane extract was dried over anhydrousNa₂SO₄, filtered, and the volatiles were removed in a rotary evaporatorto dryness to give the desired product, methyl 2,4,6-trimethoxybenzoate,as a white crystalline solid.

Step 2: Synthesis of Heptamethoxy Red

1-bromo-2,4-dimethoxybenzene (4.23 g, 19.47 mmol) was added to a roundbottom flask, and the flask flushed with nitrogen for 10 minutes.Anhydrous ether (80 mL) was added, followed by the drop wise addition ofn-butyllithium in hexane (1.6M, 12.2 mL). The cloudy mixture was stirredat room temperature for 10 minutes. Methyl 2,4,6-trimethoxybenzoate(2.20 g, 9.74 mmol) was dissolved in ether, and added drop wise to thereaction mixture. After the addition was complete, the reaction wasstirred for 3 minutes longer. The reaction was then poured into aseparatory funnel containing 5% NH₄Cl (50 mL) and shaken until a colorchange was observed. The layers were separated, and the ether layer wasdried over anhydrous Na₂SO₄, filtered, and the volatiles were removed ina rotary evaporator to dryness. The crude oil was placed in the freezer.(Crude yield 6.02 g, 132%).

Example 2 One Step Preparation of Heptamethoxy Red

Add (4.23 g, 19.47 mmol) 1-bromo-2,4-dimethoxybenzene to anappropriately sized round bottom flask. Attach a rubber septum to sealthe flask. Insert a needle into the septum as a vent and flush the roundbottom flask with nitrogen for about 10 minutes. Add (80 mL) anhydrousether, followed by the drop wise addition of n-butyllithium in hexane(1.6M, 12.2 mL). Stir the cloudy mixture for 10 minutes and keep theround bottom flask on ice. Dissolve (2.20 g, 9.74 mmol) of methyl2,4,6-trimethoxybenzoate in about 20 ml of anhydrous ether (more than˜20 mL can be used if needed), and then add this drop wise to thereaction mixture. After the addition is complete, stir the reactionmixture for about 3 minutes longer. Pour the reaction mixture into aseparatory funnel containing 5% NH₄Cl (aq) (50 mL) and shake until acolor change is observed (pale orange). The layers are allowed toseparated, and dry the top ether layer with about 5 g anhydrous Na₂SO₄,filter, and the volatiles were removed in a rotary evaporator to drynessat 35-40° C. under 400 mbar. Place the crude oil of heptamethoxy red(yellow-orange in color) into the freezer. Yield is ˜3.1 g.

Example 3 Preparation of Hexamethoxy Red in Gram Scale

Add (4.23 g, 19.47 mmol) 1-bromo-2,4-dimethoxybenzene to anappropriately sized round bottom flask. Attach a rubber septum to sealthe flask. Insert a needle into the septum as a vent and flush the roundbottom flask with nitrogen for about 10 minutes. Add anhydrous ether (80mL), followed by the drop wise addition of n-butyllithium in hexane(1.6M, 12.2 mL). Stir the cloudy mixture for 10 minutes and keep theround bottom flask on ice. Dissolve (2.20 g, 9.74 mmol) of methyl2,4-dimethoxybenzoate in about 20 ml of anhydrous ether (if needed, morethan about 20 ml can be used), and then add this drop wise to thereaction mixture. After the addition is complete, stir the reactionmixture for about 3 minutes longer. Pour the reaction mixture into aseparatory funnel containing 5% NH₄Cl (aq) (50 mL) and shake until acolor change is observed (pale orange). The layers are allowed toseparated, and dry the top ether layer with about 5 g anhydrous Na₂SO₄,filter, and the volatiles were removed in a rotary evaporator to drynessat 35-40° C. under 400 mbar. Place the crude oil of hexamethoxy red(yellow-orange in color) into the freezer. Yield is about 3.1 g.

Example 4 Preparation of a Polymerizable Indicator of this Invention

Heptamethoxy red (1 molar equivalent) is heated with an alkyl thiol(1.2-5 molar equivalents) and sodium tertiary butoxide (1.2-5 molarequivalents) in DMF (about 0.5-2 moles/liter with respect to hexamethoxyred). The reaction is monitored for disappearance of hexamethoxy redand/or formation of hydroxylated compounds. When the reaction issubstantially complete, the reaction mixture is cooled,Br—(CH₂)_(m)—OC(O)CH═CH₂, where m is 2-10 (preferably in the same molarequivalent as the thiolate), added in situ, and the reaction mixtureheated again, if necessary. The polymerizable indicator is isolated fromthe reaction mixture following aqueous work up and separated bychromatography preferably under neutral to slightly basic conditions,such as by employing neutral or basic alumina, or by employing aslightly alkaline eluent such as an eluent spiked with triethyl amine.

UTILITY

The compounds of this invention are useful as pH indicators,particularly when polymerized, such as with another monomer such ashydroxyethyl methacrylate. The pH indicators of this invention and thepolymers including the monomers of this invention are useful in contactlenses, food packaging, and bandages.

The polymerizable group is chosen relative to the polymer to be formed.For example, allyl and 2-(acryl)ethylene are readily incorporated intopolyacrylates, polymethacrylates, polymers of HEMA (2-hydroxylethylenemethacrylate), polyvinylacetate, polyvinylalcohol, polystyrene, and thelike. Because the pH indicators of this invention have beenfunctionalized to include reactive functionality similar to the monomerto be polymerized, one can form either random copolymers of the monomerand the pH indicator or block copolymers where the pH indicator islimited to a very specific part of the polymer. The latter allows only aportion of the polymer to provide pH indication.

Similarly, isocyanate and thioisocyanates are readily incorporated intopeptides and proteins through appropriate functional groups such asamino or hydroxyl functionalities as well as through carbohydrates viaone or more of their hydroxyl functionalities. In each case, acarbohydrate based wound covering such as those using cotton, hyaluronicacid, and the like can covalently couple the pH indicator directly intothe carbohydrate fiber thereby avoiding leaching of the indicator.Likewise, protein based therapeutics such as those incorporating, e.g.,collagen can likewise incorporate into the polymer.

The various polymerizable groups can also attach to nucleic acids suchas DNA and RNA, including siRNA, providing nucleic acid probes.

In addition to the above, when multiple polymerizable groups areemployed in the same molecule, the molecule can be used both as across-linking agent as well as a pH indicator thereby obviating the needfor all or some of a separate cross-linking agent if the polymer is tobe cross-linked.

1. A compound selected from the group consisting of compounds whichcompounds are represented by Formulas (I) and (II):

wherein each of p, q, and r independently are, 0, 1, or 2, provided thatthe compound of Formula (II), excludes pentamethoxy red, hexamethoxyred, and heptamethoxy red; each X is independently is: C₁-C₆ alkyl,optionally substituted with 1-3 phenyl, oxo, cyano, halo, nitro; phenylor naphthyl, optionally substituted with 1-4 substituents, wherein eachsubstituent is selected from the group consisting of alkyl, —OR¹⁸,wherein R¹⁸ is alkyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, each of which isoptionally substituted with 1-5 substituents selected from the groupconsisting of halo, cyano, C₁-C₆ alkoxy, and aryloxy; —OR¹⁹, wherein R¹⁹is hydrogen, C₁-C₆ alkyl, C₃-C₈ cycloalkyl, or phenyl, each of which isoptionally substituted with 1-5, substituents selected from the groupconsisting of halo, cyano, C₁-C₆ alkoxy, and aryloxy, or R¹⁹ is Pg; orcyano, halo, nitro; Pg is a hydroxyl protecting group; each R¹⁷independently is hydrogen or X, wherein X is defined as above; R¹ ishydrogen, X, or —OR⁸, wherein X is defined as above; each of R²-R⁸independently is hydrogen, Pg, C₁-C₄ alkyl or is -L-R⁹; R⁹ is apolymerizable group; and L is a covalent bond or a linker which joinsthe one or more polymerizable groups to the oxygen atom to which it isattached.
 2. A compound which is represented by Formula (I):

wherein each of p, q, and r independently are, 0, 1, or 2; each X isindependently is: C₁-C₆ alkyl, optionally substituted with 1-3 phenyl,oxo, cyano, halo, nitro; phenyl or naphthyl, optionally substituted with1-4 substituents, wherein each substituent is selected from the groupconsisting of alkyl, —OR¹⁸, wherein R¹⁸ is alkyl, C₃-C₈ cycloalkyl,C₆-C₁₀ aryl, each of which is optionally substituted with 1-5substituents selected from the group consisting of halo, cyano, C₁-C₆alkoxy, and aryloxy; —OR¹⁹, wherein R¹⁹ is hydrogen, C₁-C₆ alkyl, C₃-C₈cycloalkyl, or phenyl, each of which is optionally substituted with 1-5,substituents selected from the group consisting of halo, cyano, C₁-C₆alkoxy, and aryloxy, or R¹⁹ is Pg; or cyano, halo, nitro; Pg is ahydroxyl protecting group; each R¹⁷ independently is hydrogen or X,wherein X is defined as above; R¹ is hydrogen, X, or —OR⁸, wherein X isdefined as above; each of R²-R⁸ independently is hydrogen, Pg, C₁-C₄alkyl or is -L-R⁹; R⁹ is a polymerizable group; and L is a covalent bondor a linker which joins the one or more polymerizable groups to theoxygen atom to which it is attached.
 3. A compound which is representedby Formula (I-B):

wherein each of p, q, and r independently are, 0, 1, or 2, provided thatthe compound of Formula II excludes pentamethoxy red, hexamethoxy red,and heptamethoxy red; each X is independently is: C₁-C₆ alkyl,optionally substituted with 1-3 phenyl, oxo, cyano, halo, nitro; phenylor naphthyl, optionally substituted with 1-4 substituents, wherein eachsubstituent is selected from the group consisting of alkyl, —OR¹⁸,wherein R¹⁸ is alkyl, C₃-C₈ cycloalkyl, C₆-C₁₀ aryl, each of which isoptionally substituted with 1-5 substituents selected from the groupconsisting of halo, cyano, C₁-C₆ alkoxy, and aryloxy; —OR¹⁹, wherein R¹⁹is hydrogen, C₁-C₆ alkyl, C₃-C₈ cycloalkyl, or phenyl, each of which isoptionally substituted with 1-5, substituents selected from the groupconsisting of halo, cyano, C₁-C₆ alkoxy, and aryloxy, or R¹⁹ is Pg; orcyano, halo, nitro; Pg is a hydroxyl protecting group; each R¹⁷independently is hydrogen or X, wherein X is defined as above; R¹ ishydrogen, X, or —OR⁸, wherein X is defined as above; each of R²-R⁸independently is hydrogen, Pg, C₁-C₄ alkyl or is -L-R⁹; R⁹ is apolymerizable group; and L is a covalent bond or a linker which joinsthe one or more polymerizable groups to the oxygen atom to which it isattached.
 4. A compound of claim 1 which compound is represented byFormula (I-A):

wherein R¹ is hydrogen, —OH, —O—Pg, or —OR⁸; each of R²-R⁸ independentlyis hydrogen, C₁-C₄ alkyl, or is -L-R⁹ provided that at least one ofR²-R⁸ is -L-R⁸; and R⁹, Pg, and L are defined as in claim
 1. 5. Thecompound of claim 1 which compound is represented by Formula (II):

wherein each R¹⁷ independently is hydrogen or X, and X, p, q, r, and R¹⁷are defined as in claim
 1. 6. The compound of claim 1 which compound isrepresented by Formula (II-A)

where X¹-X³ are independently hydrogen or are defined as X in claim 1,and R²¹-R²³ are defined as R¹⁷ in claim
 1. 7. The compound of claim 1,wherein R¹ is hydrogen or —OR⁸; each of R²-R⁸ independently is C₁-C₄alkyl or is -L-R⁹ provided that at least one of R²-R⁸ is -L-R⁸; R⁹ is apolymerizable group; and L is a covalent bond or a linker which joinsthe one or more polymerizable groups to oxygen atoms.
 8. The compound ofclaim 1, wherein 1-7 of R²-R⁸ are -L-R⁹.
 9. The compound of claim 1,wherein 2-6 of R²-R⁸ are -L-R⁹.
 10. The compound of claim 1, wherein 1-6of R²-R⁸ is C₁-C₄ alkyl.
 11. The compound of claim 1, wherein 1-6 ofR²-R⁸ is methyl.
 12. The compound of claim 1, wherein the polymerizablegroup is selected from the group consisting of —NCO, —NCS, —N₃, ethynyl,—CO₂R¹¹,

R¹⁰ is selected from the group consisting of hydrogen, CO₂H, CO₂R¹², CN,and CON(R¹³)₂; R¹¹ is a phenyl substituted with 4 or 5 fluoro atoms, oris succinimidyl or phthalimidyl; R¹² is C₁-C₁₂ alkyl optionallysubstituted with 1-3 hydroxy groups; R¹³ is C₁-C₁₂ alkyl optionallysubstituted with 1-3 hydroxy groups or the 2 R¹³ groups together withthe nitrogen atoms they are bound to form a 5-7 membered heterocyclicring; R¹⁵ is selected from the group consisting of hydrogen, C₁-C₆ alkyloptionally substituted with 1-3 hydroxy groups, and CN; Y is O or NR¹⁶;and R¹⁶ is hydrogen or C₁-C₆ alkyl.
 13. The compound of claim 1, whereinL is C₁-C₂₀ alkylene or heteroalkylene optionally substituted with 1-10substituents selected from the group consisting of oxo (═O), thio (═S),and C₁-C₆ alkyl.
 14. The compound of claim 3 of Formula (I-C):

wherein R¹ is hydrogen or —OR²⁰; each R²⁰ independently is hydrogen,methyl, vinyl, allyl, —(CH₂)_(m)—OCOCH═CH₂, or —(CH₂)_(m)—OCOC(Me)═CH₂,provided that at least one R²⁰ is not methyl; and m is 2-10.
 15. Thecompound of claim 14, wherein each R²⁰ independently is methyl, vinyl,allyl, —(CH₂)_(m)—OCOCH═CH₂, or —(CH₂)_(m)—OCOC(Me)═CH₂, provided thatat least one R²⁰ is not methyl.
 16. The compound of claim 14, wherein 1,2, or 3 R²⁰ groups are —(CH₂)_(m)—OCOC(Me)═CH₂.
 17. The compound ofclaim 1, wherein at least one of R²-R⁸ is hydrogen or R¹ is OH.